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Biomedical subjects

A Becker

Publications and source records attributed to A Becker.

At least 541 records · Page 30Linked to original sources
PubMedDate not supplied

The anticonvulsive effect of BCH 325 is age dependent.

The two different experimental approaches which were applied to study the anticonvulsive effectiveness of BCH 325, a des-tyrosine derivative of bovine beta-casomorphin-(5), in immature (22-day-old) and mature (7-week-old) female rats revealed that the peptide was able to protect mature females from electrically induced seizures and that it had no effect on pentylenetetrazol-induced convulsions. As opposed to this, immature animals were protected against chemically induced seizures but no effect was found using electrically induced seizures.

Age Factors↗
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Influence of beta-casomorphin derivatives on chemically and electrically induced seizures.

Derivatives of beta-casomorphin(1-5) at a dose level of 1 mumol/kg body weight were tested for their influence on pentylenetetrazol, picrotoxin, or electrically induced seizures after subcutaneous injection in mice. Tyr-Pro-Phe-D-Pro-Gly was found to facilitate pentylenetetrazol-evoked seizures, whereas desTyr derivatives Pro-Phe-D-Pro-Gly and Pro-Phe-Pyr exhibited anticonvulsant properties against those convulsions. The tripeptide was effective only 10 min after application. The beta-casomorphin derivative Pro-D-Phe-Pro-Gly was effective against electrically induced seizures. The protective action of this tetrapeptide lasted for about 5 h. Additionally, we tested the influence of orally administered Pro-Phe-D-Pro-Gly on pentylenetetrazol-induced seizures and Pro-D-Phe-Pro-Gly on electrically induced seizures. Both peptides were effective at a dose of 5 mumol/kg body weight.

Amino Acid Sequence↗
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dTyr-D-Phe3 (Pro-D-Phe-Pro-Gly) interacts specifically with amygdaloid-kindled seizures and is capable of preventing the learning deficit occurring after kindling.

In amygdala-kindled rats a deficit in learning brightness discrimination was found. We concluded that this result provides a reliable basis for creating an animal model of cognitive dysfunctions in epileptics. Recently, a des-tyrosine D-amino acid substituted derivative of bovine beta-casein(1-5) was reported to exhibit anticonvulsant as well as antidepressant activity. Therefore, we tested the effect of this peptide on kindled seizures and the learning deficit after kindling. It was found that the peptide suppressed the duration of seizures whereas seizure severity was not influenced. Furthermore, the learning performance of peptide-treated rats was significantly higher than that of kindled controls.

Amygdala↗
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Low doses of AMPA exert anticonvulsant effects on pentylenetetrazol-kindled seizures.

Excitatory amino acids (EAAs) are critically involved in the initiation and propagation of seizures. N-methyl-D-aspartate (NMDA) and alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionate (AMPA) receptors appear to be of special interest in this regard. Besides receptor binding by antagonists, the function of glutamatergic synapses can be altered via autoreceptor-mediated mechanisms or by receptor desensitisation. Therefore, the effect of AMPA (1, 10 or 100 pmol per animal, intracerebroventricular injection) was tested on acutely induced pentylenetetrazol (PTZ) seizures. The lowest dose exerted clear anticonvulsant effects. Furthermore, 1 and 10 pmol AMPA were tested for their efficacy to suppress PTZ kindling. The lower dose reduced seizure severity significantly but 10 pmol AMPA was ineffective. In reaction to a test dose of PTZ, the kindled groups pretreated with AMPA reached seizure scores similar to saline-pretreated kindled rats, suggesting that the kindled state was reached. In a further experiment, we tested the effect of cyclothiazide (CYC, which blocks AMPA receptor desensitisation) on the 1 pmol AMPA-mediated anticonvulsant effect. The AMPA response was not altered. These results suggest that autoreceptor-mediated mechanisms rather than desensitisation might contribute to the anticonvulsant effect found.

Animals↗
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Synthesis, characterization, and biological properties of cyanine-labeled somatostatin analogues as receptor-targeted fluorescent probes.

We present the synthesis and characterization of the somatostatin receptor-specific peptide H(2)N-(D-Phe)-cyclo[Cys-Phe-(D-Trp)-Lys-Thr-Cys]-Thr-OH, which is labeled with a carboxylated indodicarbo- and an indotricarbocyanine dye at the N-terminal amino group. The preparation was performed by automated solid-phase synthesis, with subsequent attachment of the cyanine dye and cleavage of the entire conjugate from the resin. The compounds display high molar absorbance and fluorescence quantum yields typical for cyanine dyes and are thus suitable receptor-targeted contrast agents for molecular optical imaging. The ability of these agents to target the somatostatin receptor was demonstrated by flow cytometry in vitro, in which the indotricarbocyanine conjugate led to elevated cell-associated fluorescence on somatostatin receptor-expressing tumor cells. In contrast, the corresponding linearized derivative of the sequence H(2)N-(D-Phe)-Met-Phe-(D-Trp)-Lys-Thr-Met-Thr-OH produced only minimal cell fluorescence, hence confirming the specificity of the cyclic somatostatin analogue. Intracellular localization could be visualized by near-infrared (NIR) fluorescence microscopy. In conclusion, receptor-specific peptides are promising tools for designing site-directed optical contrast agents for use in molecular optical imaging.

Animals↗
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Tumour induction by the retinoblastoma mutation is independent of N-myc expression.

Retinoblastoma (RB) tumours form in the eyes of young children when homozygosity for a mutation at the Rb-1 locus develops in a somatic retinal cell. A similar shift to homozygosity for the RB mutation has been observed in osteogenic sarcoma (OS) tumours that commonly arise as second tumours in children who survive RB. This observation suggests that the Rb-1 locus controls the expression of genes with oncogenic potential; a possible target is the oncogene N-myc, which is sometimes amplified and over-expressed in the neuroectodermal tumours neuroblastoma and RB. However, N-myc is developmentally regulated in normal murine embryogenesis, and an alternative possibility is that the expression of the gene in tumour cells reflects their embryonic origin and is unrelated to the RB mutation. We have therefore examined N-myc expression in various fetal, adult and tumour tissues, and report here that the gene is expressed in fetal but not in adult brain and retina and in near-diploid RB tumour samples at levels similar to those observed in normal fetal retina. Only RB tumours with genomic amplification of the N-myc gene exhibited increased levels of expression; and no N-myc transcripts were detected in osteogenic sarcomas initiated by mutations at the Rb-1 locus. We therefore conclude that the expression of N-myc in RB tumours probably reflects the origin of the tumour from an embryonic tissue normally expressing the gene and is not directly associated with the mutation at the RB locus.

Animals↗
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Dominance of one T-cell receptor in the H-2Kb/TNP response.

T-cell receptors (TCRs) recognize foreign antigens in the context of major histocompatibility complex (MHC)-encoded cell surface proteins. These receptors are heterogeneous, dimeric glycoproteins composed of disulphide linked alpha- and beta-chains. We analysed the diversity of TCRs in a collection of H-2Kb-restricted, 2,4,6-trinitrophenyl (TNP)-specific (H-2Kb/TNP) cytotoxic T-cell (Tc) clones from C57BL/6 mice. Investigation of the beta-chain messenger RNAs revealed that nearly half of these independent clones expressed an identical beta-chain gene. We show here that almost all the Tc clones expressing the predominant beta-chain gene also express an identical alpha-chain gene. These results show that a strong selective pressure acted on the Tc population, resulting in a skewing of the TCR repertoire for H-2Kb/TNP and in the dominant expression of one TCR with this specificity. Possible explanations for this skewing include antigen-driven clonal expansion and network interactions.

Animals↗
PubMedDate not supplied

[Guidelines for back pain].

Chronic back pain is one of our society's most important health problems, causing long periods of sick leave and early retirements. Recently the German Society of General Practice and Family Medicine (DEGAM) published an evidence-based guideline for low back pain. It has been developed according to the 10-step concept of guideline development of the DEGAM, aiming for early detection of complicated clinical conditions, avoidance of unnecessary diagnostic tests and prevention of chronicity. Complicated, uncomplicated and radicular pain are defined by patient history and a short clinical examination. Imaging and further diagnostic tests are reserved for patients at risk. Basic therapy consists of structured advice. The aim of the guideline is to get patients back to their usual activity supported by effective pain relief. Psychosocial factors which are important for the prognosis should be evaluated already during the first consultation. Manual therapy might help in acute pain. Patients with persistent pain symptoms and long periods of sick leave should be transferred to multiprofessional management including pain treatment, behavioural therapy and physiotherapy. A randomised controlled trial has been set up to study the efficacy of guideline implementation.

Activities of Daily Living↗
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Analysis of the Rhizobium meliloti genes exoU, exoV, exoW, exoT, and exoI involved in exopolysaccharide biosynthesis and nodule invasion: exoU and exoW probably encode glucosyltransferases.

Sequence analysis of a 5.780-kb DNA fragment originating from megaplasmid 2 of Rhizobium meliloti 2011 involved in biosynthesis of exopolysaccharide I (EPS I) and invasion of alfalfa nodules revealed the presence of five exo genes designated exoU, exoV, exoW, exoT, and exoI. ExoT resembled transmembrane proteins, whereas ExoI displayed a characteristic signal peptide. Sequence comparisons with several polysaccharide-polymerizing enzymes of both prokaryotic and eukaryotic origin indicated that exoW and exoU encode glucosyltransferases. Moreover, ExoV displayed weak homologies to the ExoO, ExoA, ExoL, and ExoM proteins of R. meliloti, which are also discussed as glucosyltransferases. Using exo-lacZ transcription fusions in connection with plasmid integration mutagenesis, promoters were identified in front of exoI, exoT, exoW, exoV, and exoU.R. meliloti 2011 strains with mutations in exoT, exoW, exoV, and exoU produced no detectable EPS I and were unable to infect alfalfa nodules, whereas exoI mutants synthesized a reduced amount of EPS I and did infect alfalfa nodules.

Amino Acid Sequence↗
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The management of drooling problems in children with neurological dysfunction: a review and case report.

Drooling in children with neurological dysfunction indicates neurogenic failure to coordinate the muscles of the tongue, soft palate, and face which act in the first stage of swallowing. This causes excessive pooling of saliva in the anterior part of the mouth and consequent overspill. Treatment for drooling includes behavioral, pharmacological, and surgical modalities. Correcting a malocclusion has also been reported to help eliminate drooling. This paper describes the treatment of a child with neurofibromatosis, psychomotor, developmental, and neurologic retardation, and difficulty with speech. The patient was referred to our clinic to correct his drooling. Simple orthodontic treatment succeeded in eliminating the drooling and improving his speech.

Child↗
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A case-control study of the role of cold symptoms and other historical triggering factors in asthma exacerbations.

BACKGROUND: Asthma exacerbations can be provoked by many triggers such as allergens, respiratory irritants and viral infections. The relative importance of these has not been prospectively documented in a case-control study. OBJECTIVE: To assess the relative importance of colds and other nonclimatic historical triggers of asthma exacerbations. METHODS: One hundred and nineteen adults and children with asthma in two Canadian cities participated in a one-year study of the role of exacerbating factors in asthma. Among these, 36 pairs (21 adult, 15 children) completed the case-control study. Patients were considered cases if they developed an acute asthma exacerbation and notified the centre within 24 h to allow the completion of a questionnaire and viral studies (cultures of nasopharyngeal swabs and serology). Control people with asthma were matched for sex, age and area of residence, had no exacerbation during the preceding four weeks and participated within 48 h of the case patients. RESULTS: Case patients versus control patients had a mean age of 22 years versus 20 years, 50% versus 55% were male, and 92% versus 86% had at least one positive aeroallergen skin test. Cases were more likely to have taken regular inhaled steroids (63% versus 33%, P<0.002). Cases were more likely to report the following within the previous week: fever (P<0.001), sore throat (P<0.001), increase in nasal symptoms (P<0.01), increased dust exposure (P<0. 05), exposure to others with a cold (P<0.001) and, over the previous year, increased passive smoke exposure (P<0.05). Viral cultures and paired serology were negative. CONCLUSIONS: Symptomatic colds were the most common trigger of asthma exacerbations in the winter and spring, while a transient increase in dust exposure was also identified as a significant trigger. The association with chronic, passive smoke exposure and the use of inhaled costicosteroid medications likely reflected less stable pre-study asthma in those with exacerbations.

Adult↗
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What is new since the last (1999) Canadian Asthma Consensus Guidelines?

The objective of the present document is to review the impact of new information on the recommendations made in the last (1999) Canadian Asthma Consensus Guidelines. It includes relevant published studies and observations or comments regarding what are considered to be the main issues in asthma management in children and adults in office, emergency department, hospital and clinical settings. Asthma is still insufficiently controlled in a large number of patients, and practice guidelines need to be integrated better with current care. This report re-emphasises the need for the following: objective measures of airflow obstruction to confirm the diagnosis of asthma suggested by the clinical evaluation; identification of contributing factors; and the establishment of a treatment plan to rapidly obtain and maintain optimal asthma control according to specific criteria. Recent publications support the essential role of asthma education and environmental control in asthma management. They further support the role of inhaled corticosteroids as the mainstay of anti-inflammatory therapy of asthma, and of both long acting beta2-agonists and leukotriene antagonists as effective means to improve asthma control when inhaled corticosteroids are insufficient. New developments, such as combination therapy, and recent major trials, such as the Children's Asthma Management Project (CAMP) study, are discussed.

Adrenergic beta-Agonists↗
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Automatic selection of loop breakers for genetic linkage analysis.

Pedigree loops pose a difficult computational challenge in genetic linkage analysis. The most popular linkage analysis package, LINKAGE, uses an algorithm that converts a looped pedigree into a loopless pedigree, which is traversed many times. The conversion is controlled by user selection of individuals to act as loop breakers. The selection of loop breakers has significant impact on the running time of the subsequent linkage analysis. We have automated the process of selecting loop breakers, implemented a hybrid algorithm for it in the FASTLINK version of LINKAGE, and tested it on many real pedigrees with excellent performance. We point out that there is no need to break each loop by a distinct individual because, with minor modification to the algorithms in LINKAGE/FASTLINK, a single individual that participates in multiple marriages can serve as a loop breaker for several loops. Our algorithm for finding loop breakers, called LOOPBREAKER, is a combination of: (1) a new algorithm that is guaranteed to be optimal in the special case of pedigrees with no multiple marriages and (2) an adaptation of a known algorithm for breaking loops in general graphs. The contribution of this work is the adaptation of abstract methods from computer science to a challenging problem in genetics.

Algorithms↗
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Pharmacodynamic effects of 3-day intravenous treatment with pantoprazole or ranitidine after 10 days of oral ranitidine.

Tachyphylaxis (drug tolerance) is an undesirable condition in drug therapy with histamine-2-receptor antagonists (H2RAs). The concept of overcoming tachyphylaxsis via intravenous (i.v.) administration of proton-pump inhibitors (PPIs) or H2RAs is of significant interest to physicians. In the present study, 32 healthy Helicobacter pylori negative male volunteers were evaluated for the ability of i.v. pantoprazole or i.v. ranitidine to overcome oral ranitidine tachyphylaxis. After 10 days of oral treatment with enteric-coated 300-mg ranitidine tablets once daily in the evening, two groups of 16 volunteers each were randomized to receive either i.v. pantoprazole or i.v. ranitidine for up to 72 h. The primary variable was defined as the increase in 24-h gastric pH median after 1 day of i.v. treatment; the secondary variable was median percentage of time that 24-h gastric pH was <4, as calculated by Hodges-Lehman shift estimators. After 10 days of oral ranitidine treatment, tachyphylaxis was present in all volunteers. Within 1 day of continuous i.v. pantoprazole or i.v. ranitidine administration, 24-h median gastric pH increased from pH 1.45 to pH 3.50 (241%) and from pH 1.50 to pH 2.35 (157%), respectively. I.v. pantoprazole was found to be significantly more effective (p<0.05) than i.v. ranitidine in increasing the 24-h gastric pH after oral ranitidine tachyphylaxis.

2-Pyridinylmethylsulfinylbenzimidazoles↗
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Clinical utility of quantitative assessment of liver haemodynamics in cirrhosis provided by dynamic hepatoscintigraphy.

Interrelationships between quantitative assessment of portal (%Qp) and arterial (%Qa) components of hepatic blood supply obtained by dynamic hepatoscintigraphy, and clinical variables characterizing the severity of liver cirrhosis and portal hypertension were studied in 25 cirrhotic patients. The variables, clinical state, size of oesophageal varices, ascites accumulation, sonographic stigmata of portal hypertension, liver mass and elimination rate of lidocaine and antipyrine were studied. The %Qa rose in proportion to the severity of liver injury estimated from the Child-Turcotte and McCormick grading scores. The mean %Qa for patients with Child A cirrhosis was significantly higher than that for 8 healthy subjects (34.8 +/- 7.9% vs 18.1 +/- 4.0; P < 0.01). The %Qp values showed relationship with the size of esophageal varices, provided discriminatory data with respect to the ascitic fluid accumulation and the development of intraabdominal collateral circulation. The liver mass had no impact on hepatic dual blood supply pattern, but was linked with the rate of antipyrine clearance. Neither antipyrine clearance nor lidocaine elimination rate corresponded to alterations of hepatic dual blood supply. The %Qp showed a negative correlation with the initial half-life of lidocaine, which was referred to lowered hepatic uptake of the drug. It is concluded that the quantitative assessment of %Qp and %Qa reflect the advancement of portal hypertension better than liver function failure does.

Adult↗